Patients with multipe sclerosis, spinal cord trauma, amyotrphic lateral sclerosis and other neurologic illnesses are often disabled by flexor spasms, hyperreflexia and increased tone. The neuronal mechanisms underlyig these abnormalities are poorly understood, however the removal of spinal cord inhibitory interneurons from supraspinal control may explain some of these symptoms of spasticity. We are measuring a) the endogenous levels of GABA, glucine, norepinephrine and serotonin b) the inactivation of these transmitters by high affinity reuptake mechanisms and c) the synaptic receptors for these transmitters during thedevelopment of spasticity after high spinal cord transection in the rat. These biochemical variables are being correlated with the clinical development of spasticity. During the flaccid stage after spinal cord transection, we have found significant increases in the number of high affinity reuptake sites for GABA with no change in glycine reuptake and a signficiant reduction in norephinephrine reuptake. Levels of GABA and norepinephrine are also reduced during the flaccid stage, but no change has been noted in synaptic receptors for thesr transmitters. We are currently defining the time course of these changes in more detail and attempting to assess which supraspinal pathways are responsible for the changes. We are also reassessing receptor sensitivities on subregions of spinal cord during the development of spasticity.